Modeling antibody dynamics following herpes zoster indicates that higher varicella-zoster virus viremia generates more VZV-specific antibodies

Frontiers in Immunology

Immunology

Irene Garcia-Fogeda¹  Philippe Beutels¹  Hajar Besbassi²  Benson Ogunjimi³  Niel Hens⁴  Judy Breuer⁵  Mark Quinlivan⁵  Steven Abrams⁶ 

[1] Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium;Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium;Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium;Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium;Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium;Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing (AUDACIS), University of Antwerp, Antwerp, Belgium;Antwerp Center for Translational Immunology and Virology (ACTIV), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium;Department of Paediatrics, Antwerp University Hospital, Edegem, Belgium;Centre for Health Economics Research and Modeling Infectious Diseases (CHERMID), Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium;Data Science Institute (DSI), Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BioStat), UHasselt, Hasselt, Belgium;Division of Infection and Immunity, University College London, London, United Kingdom;Global Health Institute (GHI), Family Medicine and Population Health (FAMPOP), University of Antwerp, Antwerp, Belgium;Data Science Institute (DSI), Interuniversity Institute for Biostatistics and Statistical Bioinformatics (I-BioStat), UHasselt, Hasselt, Belgium;

关键词: varicella zoster virus;    herpes zoster;    antibody levels;    ordinary differential equations;    nonlinear mixed-effects models;    mathematical modeling;   

DOI  :  10.3389/fimmu.2023.1104605

 received in 2022-11-21, accepted in 2023-01-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionStudying antibody dynamics following re-exposure to infection and/or vaccination is crucial for a better understanding of fundamental immunological processes, vaccine development, and health policy research.MethodsWe adopted a nonlinear mixed modeling approach based on ordinary differential equations (ODE) to characterize varicella-zoster virus specific antibody dynamics during and after clinical herpes zoster. Our ODEs models convert underlying immunological processes into mathematical formulations, allowing for testable data analysis. In order to cope with inter- and intra-individual variability, mixed models include population-averaged parameters (fixed effects) and individual-specific parameters (random effects). We explored the use of various ODE-based nonlinear mixed models to describe longitudinally collected markers of immunological response in 61 herpes zoster patients.ResultsStarting from a general formulation of such models, we study different plausible processes underlying observed antibody titer concentrations over time, including various individual-specific parameters. Among the converged models, the best fitting and most parsimonious model implies that once Varicella-zoster virus (VZV) reactivation is clinically apparent (i.e., Herpes-zoster (HZ) can be diagnosed), short-living and long-living antibody secreting cells (SASC and LASC, respectively) will not expand anymore. Additionally, we investigated the relationship between age and viral load on SASC using a covariate model to gain a deeper understanding of the population’s characteristics.ConclusionThe results of this study provide crucial and unique insights that can aid in improving our understanding of VZV antibody dynamics and in making more accurate projections regarding the potential impact of vaccines.

【 授权许可】

Unknown   
Copyright © 2023 Besbassi, Garcia-Fogeda, Quinlivan, Breuer, Abrams, Hens, Ogunjimi and Beutels